Adrenal Agents Flashcards
What are the functions of
Mineralocorticoids:
Glucocorticoids:
Androgens:?
Mineralocorticoids: regulate volume via Na and K
Glucocorticoids: Restoring homeostasis after exposure to stresses
Androgens: DHEA/Androstenedione - converted to Testosterone in peripheral tissues
What are common targets for drugs?
11 beta hydroxylase - METYRAPONE blocks
17 alpha hydroxylase - KETOCONAZOLE blocks
21 hydroxylase is also ok
what is unique about Mineralocorticoid receptors and glucocorticoid receptors?
BOTH are nuclear hormone receptors,
glucocorticoids/mineralocorticoids cross membrane and cause these to enter nucleus and affect transcription
CORTISOL binds BOTH MR and GR
What are the ANTIINFLAMMATORY effects of Glucocorticoids?
Inhibit PHOSPHOLIPASE A - Decreased Prod of prostaglandins and Leukotrienes
Inhibit COX2 synthesis - Decrease prostaglandins
Inhib CYTOKINE production: suppress cell-mediated inflammation
Reduce number/activity of MAST CELLS: dec histamine and 5HT, decrease capillary permeability
What is 11 beta HSD-1 and 11 Beta HSD-2?
11B HSD-1: in liver: converts cortisone to cortisol
11B HSD-2: in kidney: converts cortisol to cortisone
Cortisol is active at GR and MR
Cortisone is INACTIVE at GR and MR
At high doses of cortisol, 11B HSD-2 can be saturated and levels are high/not able to be broken down
ALSO, high cortisol can have effect at Mineralocorticoid receptors
Out of the commonly used Glucocorticoids, which have Salt retaining effects, and which dont?
DO have Na retention:
CORTISOL (CORTISONE is prodrug)
PREDNISOLONE (PREDNISONE is prodrug)
DO NOT have Na retention
TRIAMCINOLONE
BETAMETHASONE
DEXAMETHASONE
Out of the commonly used Glucocorticoids, which are long acting/short acting?
Short acting: CORTISOL
Intermediate acting: PREDNISOLONE, TRIAMCINOLONE
Long acting: BETAMETHASONE, DEXAMETHASONE
Pharmacokinetics of Glucocorticoids
over 90% is bound in serum
remaining free cortisol is active
Individuals with liver dz may have less binding protein production and therefor need a smaller dose
Inactivated by CYP450 enzymes and excreted in urine
What are the adverse effects of Glucocorticoids?
Decreased GROWTH, glaucoma, central fat distribution, osteoporosis, Inc risk for INFECTION, Inc risk for diabetes, Inc appetite, Emotional disturbance, HYPOKALEMIA, HYPERTENSION, HPA AXIS SUPPRESSION (may take 12 months to return to normal - taper slowly, use short acting, lowest dose possible, single AM dose, limit length of therapy)
what are drug interactions with glucocorticoids?
NSAIDS with Glucocorticoids can cause stomach ulcers
Glucocort can dec effectiveness of hypoglycemic, b/p, and glaucoma meds (think of the adverse effects here - inc risk for diabetes, hypertension, and glaucoma)
What is the treatment for Primary Adrenal Insufficiency (Addison’s Disease)?
Oral CORTISOL - increase dose during stress
FLUDRICORTISONE - Synthetic Aldosterone
Dosed: 2/3 in the morning, 1/3 in the afternoon
Supplemented in cases of surgery to mimic bodies natural response
What is the treatment for Secondary Adrenal Insufficiency? (pituitary or hypothalamus)
CORTISOL orally
FLUDRICORTISONE is NOT NEEDED
2/3 in morn, 1/3 in afternoon - Prevent Hypotension and shock
How does High dose Dexamethasone help to determine cause of cushings disease?
Think of DEXAMETHASONE acting only on the pituitary – So if the ACTH is coming from the lung – wont be affected at all
Given High Dose Dexamethasone
Pituitary Hypersecretion: Will see a 50% decrease in Cortisol production
Adrenal Adenoma: No reduction in cortisol
Ectopic ACTH prod: No reduction in cortisol
What are the adrenocortical hormone SYNTHESIS INHIBITORS?
METYRAPONE: inhibits 11B-hydroxylase
KETOCONAZOLE: Inhibits 17 alpha-hydroxylase. liver toxic
Used to treat cushings disease
MIFEPRISTONE
Anti-progestin - terminate pregnancy
at higher dose - glucocorticoid Receptor ANTAGONIST
used to treat INOPERABLE PNTS WITH ECTOPIC ACTH SECRETION
